We propose that CD4+CD3− cells have two functions: a well-established role in organizing lymphoid tissue during development, and a newly discovered role in supporting T-cell help for B cells both during affinity maturation in germinal centres and for memory antibody responses. As CD4+CD3− cells express the HIV co-receptors CD4 and CXC-chemokine receptor 4, we think that infection of these cells by HIV, and their subsequent destruction by the host immune system, could help to explain the loss of memory antibody responses and the destruction of lymphoid architecture that occur during disease progression to AIDS.
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This work was supported by the Wellcome Trust (United Kingdom). We thank I. MacLennan, F. McConnell and G. Anderson for reading the manuscript and providing many helpful comments. We also thank C. Raykundalia, who organized us and made sure that everything in the laboratory worked.
The authors declare no competing financial interests.
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