Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro

Aruna Seth; Mitzi Nagarkatti; Prakash S. Nagarkatti; Bondada Subbarao; Venkatachalam Udhayakumar

doi:10.1016/0047-6374(90)90118-Y

Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro

Aruna Seth, Mitzi Nagarkatti, Prakash S. Nagarkatti, Bondada Subbarao, Venkatachalam Udhayakumar

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

In the present study the effect of aging on the capacity of Ia⁺ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4⁺ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia⁺ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4⁺ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells.

Original language	English
Pages (from-to)	107-124
Number of pages	18
Journal	Mechanisms of Ageing and Development
Volume	52
Issue number	2-3
DOIs	https://doi.org/10.1016/0047-6374(90)90118-Y
State	Published - Mar 15 1990

Bibliographical note

Funding Information:
In the present study the effect of aging on the capacity of Ia÷cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4 ÷ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia ÷ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-10could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4 ÷ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells "1 Supported in part by the NIH grants CA45009 and CA45010 to P.N. and M.N., and AI 21490, AG-05731 to B.S. who is also the recipient of a Research Career Development award, AG 00422. Address all correspondence to: Dr. Prakash S. Nagarkatti, Dept. of Biology, Derring Hall, Virginia Polytechnic Institute and State University Blacksburg, VA 24061, U.S.A. Abbreviations: SMLR: syngeneic mixed lymphocyte reaction: AMLR: autologous mixed lymphocyte reaction; SAC: splenic adherent cells; FITC: fluorescein isothiocyanate; IL-1 interleukin-1; rIL-l: recombinant interleukin-1.

Funding

In the present study the effect of aging on the capacity of Ia÷cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4 ÷ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia ÷ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-10could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4 ÷ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells "1 Supported in part by the NIH grants CA45009 and CA45010 to P.N. and M.N., and AI 21490, AG-05731 to B.S. who is also the recipient of a Research Career Development award, AG 00422. Address all correspondence to: Dr. Prakash S. Nagarkatti, Dept. of Biology, Derring Hall, Virginia Polytechnic Institute and State University Blacksburg, VA 24061, U.S.A. Abbreviations: SMLR: syngeneic mixed lymphocyte reaction: AMLR: autologous mixed lymphocyte reaction; SAC: splenic adherent cells; FITC: fluorescein isothiocyanate; IL-1 interleukin-1; rIL-l: recombinant interleukin-1.

Funders	Funder number
National Institutes of Health (NIH)	AI 21490, CA45010, AG 00422, AG-05731
National Childhood Cancer Registry – National Cancer Institute	R29CA045009

Keywords

Aging
Autoreactive T cells
B cells
Immune-defect
Interleukin-1
Macrophages

ASJC Scopus subject areas

Aging
Developmental Biology

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10.1016/0047-6374(90)90118-Y

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@article{8b679a08a4c6427ca1bbf37d7a6851bc,

title = "Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro",

abstract = "In the present study the effect of aging on the capacity of Ia+ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4+ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia+ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4+ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells.",

keywords = "Aging, Autoreactive T cells, B cells, Immune-defect, Interleukin-1, Macrophages",

author = "Aruna Seth and Mitzi Nagarkatti and Nagarkatti, {Prakash S.} and Bondada Subbarao and Venkatachalam Udhayakumar",

note = "Funding Information: In the present study the effect of aging on the capacity of Ia÷cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4 ÷ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia ÷ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-10could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4 ÷ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells {"}1 Supported in part by the NIH grants CA45009 and CA45010 to P.N. and M.N., and AI 21490, AG-05731 to B.S. who is also the recipient of a Research Career Development award, AG 00422. Address all correspondence to: Dr. Prakash S. Nagarkatti, Dept. of Biology, Derring Hall, Virginia Polytechnic Institute and State University Blacksburg, VA 24061, U.S.A. Abbreviations: SMLR: syngeneic mixed lymphocyte reaction: AMLR: autologous mixed lymphocyte reaction; SAC: splenic adherent cells; FITC: fluorescein isothiocyanate; IL-1 interleukin-1; rIL-l: recombinant interleukin-1.",

year = "1990",

month = mar,

day = "15",

doi = "10.1016/0047-6374(90)90118-Y",

language = "English",

volume = "52",

pages = "107--124",

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TY - JOUR

T1 - Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro

AU - Seth, Aruna

AU - Nagarkatti, Mitzi

AU - Nagarkatti, Prakash S.

AU - Subbarao, Bondada

AU - Udhayakumar, Venkatachalam

N1 - Funding Information: In the present study the effect of aging on the capacity of Ia÷cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4 ÷ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia ÷ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-10could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4 ÷ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells "1 Supported in part by the NIH grants CA45009 and CA45010 to P.N. and M.N., and AI 21490, AG-05731 to B.S. who is also the recipient of a Research Career Development award, AG 00422. Address all correspondence to: Dr. Prakash S. Nagarkatti, Dept. of Biology, Derring Hall, Virginia Polytechnic Institute and State University Blacksburg, VA 24061, U.S.A. Abbreviations: SMLR: syngeneic mixed lymphocyte reaction: AMLR: autologous mixed lymphocyte reaction; SAC: splenic adherent cells; FITC: fluorescein isothiocyanate; IL-1 interleukin-1; rIL-l: recombinant interleukin-1.

PY - 1990/3/15

Y1 - 1990/3/15

N2 - In the present study the effect of aging on the capacity of Ia+ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4+ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia+ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4+ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells.

AB - In the present study the effect of aging on the capacity of Ia+ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4+ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia+ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4+ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells.

KW - Aging

KW - Autoreactive T cells

KW - B cells

KW - Immune-defect

KW - Interleukin-1

KW - Macrophages

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Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro

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