Functional Heterogeneity of L3T4+ T Cells in MRL-lpr/lpr Mice. L3T4+ T Cells Suppress Major Histocompatibility Complex-self-restricted L3T4+ T Helper Cell Function in Association with Autoimmunity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1988 Dec 1

PMID 2974064

Citations 12

Authors

C S Via

G M Shearer

Affiliations

Soon will be listed here.

Abstract

The present study demonstrates in MRl-lpr/lpr autoimmune mice an age-dependent loss of MHC-self-restricted function by L3T4+ Th. This defect is not present in age-matched, congenic MRL-+/+ spleen cells and appears to be due to the presence of suppressor cells that are selective for L3T4+ Th and not for Lyt-2+ Th. Surprisingly, the suppressor cells are also L3T4+ T cells and can suppress the IL-2 production of congenic MRL/+ L3T4+ Th to MHC-self-restricted antigens. These data support the idea of functional specialization within the L3T4+ population of T cells. Because L3T4+ suppressor cells are detected late in the course of autoimmunity, we interpret their presence not as a primary initiating event in the development of autoimmunity, but rather as a compensatory mechanism. Additionally, similar suppression of L3T4+ Th function has also been reported in a murine graft-vs.-host model of autoimmunity, suggesting that the suppressor cells represent an immunoregulatory mechanism that is a common feature of autoimmunity. Since excessive class II-restricted Th activity for B cells has been reported for both models of autoimmunity, L3T4+ suppressor cells may represent an attempt to down regulate such excessive Th activity. These findings may be relevant to human autoimmune diseases, such as systemic lupus erythematosus, in which B cell hyperactivity is also associated with reduced IL-2 production by Th.

Citing Articles

Sex differences in donor T cell targeting of host splenocyte subpopulations in acute and chronic murine graft-vs.-host disease: implications for lupus-like autoimmunity.

Soloviova K, Via C bioRxiv. 2024; .

PMID: 38915570 PMC: 11195085. DOI: 10.1101/2024.06.07.595177.

Both perforin and FasL are required for optimal CD8 T cell control of autoreactive B cells and autoantibody production in parent-into-F1 lupus mice.

Soloviova K, Puliaiev M, Puliaev R, Puliaeva I, Via C Clin Immunol. 2018; 194:34-42.

PMID: 29940333 PMC: 6089648. DOI: 10.1016/j.clim.2018.06.007.

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a....

Soloviova K, Puliaiev M, Haas M, Dalgard C, Schaefer B, Via C J Immunol. 2015; 195(7):2985-3000.

PMID: 26320249 PMC: 4575913. DOI: 10.4049/jimmunol.1402782.

Advances in lupus stemming from the parent-into-F1 model.

Via C Trends Immunol. 2010; 31(6):236-45.

PMID: 20362509 PMC: 2883015. DOI: 10.1016/j.it.2010.02.001.

Defective in vitro IL-2 production in lupus is an early but secondary event paralleling disease activity: evidence from the murine parent-into-F1 model supports staging of IL-2 defects in human lupus.

Via C, Shearer G Autoimmunity. 2009; 43(1):23-31.

PMID: 20001649 PMC: 3215295. DOI: 10.3109/08916930903374808.

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