Absolute macrophage dependency of T lymphocyte activation by mitogens

D. L. Rosenstreich, J. J. Farrar, S. Dougherty

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293 Scopus citations


A T lymphocyte subpopulation that contains only 0.3% macrophages and less than 2% B lymphocytes was prepared from guinea pig lymph node cells by the use of two different types of adherence columns. This subpopulation does not proliferate in response to the mitogens Con A or PHA unless additional macrophages are added. The means by which macrophages restore T cell responsiveness to PHA was investigated. Macrophages appear to function via two distinct mechanisms in this experimental situation. The first mechanism involves the binding of PHA to the macrophage followed by the 'presentation' of the mitogen to the T lymphocyte in a manner that induces cell activation. This presentation function requires that the macrophage be viable and metabolically active. The second mechanism by which macrophages function is by the elaboration of a soluble factor or factors. The presence of these factors has been reliably and reproducibly demonstrated by using a double chambered, Marbrook type tissue culture vessel. This soluble factor can induce activation of T lymphocytes with surface bound PHA in the apparent absence of any form of macrophage presentation. In contrast, the function of this factor is clearly distinct from that of the reducing agent, 2 mercaptoethanol, which does not enable this T cell subpopulation to be activated by mitogens. On the basis of these observations it is suggested that two distinct signals are required to activate this T lymphocyte subpopulation. One signal is delivered by the interaction of the mitogen with the T cell surface, and the second signal is delivered by a soluble factor(s) produced by macrophages. Whether all types of T lymphocytes require two signals to be activated, remains to be established.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalJournal of Immunology
Issue number1
StatePublished - Dec 1 1976
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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