Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta.
The synthesis of antiviral beta-chemokines has joined cytolysis as a potential mechanism for the control of HIV-1 infection by CD8(+) T cells. Recent evidence suggests that these two effector functions can diverge in some individuals infected with HIV-1; however, little is known about the CD8(+) T cell subsets in normal individuals that synthesize antiviral beta-chemokines. In this report, we have used mutliparameter flow cytometry to characterize the T cell subsets that secrete the antiviral beta-chemokine macrophage inflammatory protein (MIP)-1beta. These studies have shown: (i) CD8(+) cells are the predominant T cell subset that synthesizes MIP-1beta; (ii) MIP-1beta and IFN-gamma are synthesized congruently in most CD8(+) T cells; however, significant numbers of these cells synthesize only one of these effector molecules; (iii) approximately 60% of the CD8(+) T cells that synthesize MIP-1beta lack perforin; (iv) MIP-1beta is synthesized with approximately equal frequency by CD28(+) and CD28(-) subpopulations of CD8(+) T cells; (v) MIP-1beta is synthesized by three distinct CD8(+) T cell subsets defined by the expression of CD45R0 and CD62L; and (vi) MIP-1beta is not synthesized in short-term cultures of naive CD8(+) T cells. These results demonstrate substantial subset heterogeneity of MIP-1beta synthesis among CD8(+) T cells and suggest that these subsets should be evaluated as correlates of protective immunity against HIV-1.
Kamin-Lewis
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R
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. kaminlew@umbi.umd.edu
Abdelwahab
S F
SF
Trang
C
C
Baker
A
A
DeVico
A L
AL
Gallo
R C
RC
Lewis
G K
GK
D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054407:Chemokine CCL4; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
D018106:CD28 Antigens; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma